Developments in magnetic resonance imaging now allow multidimensional assessment of the characteristics of white matter in patients with schizophrenia. Diffusion tensor imaging (DTI), which permits inferences about the coherence of white matter tracts (anisotropy), and magnetization transfer imaging (MTI), which provides a quantitative measure of macromolecular structural integrity, offer complementary views of myelin organization and integrity. Our earlier published research has indicated defects in anisotropy in frontal white matter areas in patients with schizophrenia and pilot data included in this proposal indicate abnormalities using MTI as well. In an extension of these promising results, we will acquire DTI, MTI and structural MRI images with our new 3 Tesla scanner on a new cohort of 60 young first-break schizophrenic patients and 60 chronic schizophrenic patients with a lifespan age range. These patients will be rescanned at the end of the proposal period to provide longitudinal information. A normal comparison group will have similar baseline and follow-up imaging. In addition, a cohort of approximately 120 schizophrenic patients (age 13-60), already scanned at 1.5 Tesla, will receive a clinical follow-up to provide a second independent longitudinal study. We will examine the relationship of these white matter measures to the patients' symptom severity, cognitive performance, and functional status assessed by Core B. We hypothesize that white matter abnormalities will be more marked in the prefrontal and middle temporal than inferior occipital regions. Similarity between DTI and MTI images will be examined statistically. Lastly, we will examine the relationship between choline, myo-inositol, and N-acetylaspartate from spectroscopy studies (Project 5, Chang) and regional white matter DTI and MTI measures from the same regions.